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JAMA Publishes Pro/Con Opinions on LDT Regulation in Advance of FDA Workshop

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JAMA published two Online First opinion pieces on January 5, covering each side of the proposed FDA regulation of LDTs.

Pro-Regulation Opinion

The opinion in favor of FDA regulation was written by Joshua Sharfstein, MD, from the Department of Health and Hygiene. Dr. Sharfstein’s editorial was unique among recent articles and discussions in favor of regulation in its citation of new examples of potentially faulty LDTs.

The first example cited was a 2014 warning notice from CDC regarding “serious concerns” about the potential for false positive results from a new method for culturing samples for Lyme disease testing. While the concerns may well be valid, they are not substantiated by any data to demonstrate that the test in question does in fact result in excessively high false positives.

The other specific example provided by Dr. Sharfstein is of a cardiovascular test, originally developed by Celera (but now offered by Quest Diagnostics via its 2011 acquisition Celera) that utilizes a biomarker called KIF6 to predict risk of coronary artery disease (CAD), and the potential for positive response from statin treatments.

KIF6’s utility in these contexts was called into question in a 2010 article published in the Journal of the American College of Cardiology, in which the authors claim that the test’s validation studies probably suffered from an excessive number of false positives due to the studies’ use of an antiquated methodology. The authors also cited clinical and GWAS studies that found no correlation between KIF6 and CAD risk, and the biomarker’s utility was further challenged due its lack of mechanistic associations with lipid metabolism and cardiovascular disease processes. KIF6 was also stated to lack “consistent expression…in relevant tissues such as the vasculature.” As of the article’s 2010 publication date, it was stated that >160,00 tests using KIF6 had been ordered. Statin treatment is not without side effects, so it would indeed be troublesome if an unacceptable number of patients received statins unnecessarily due to false positive results from this test.

Dr. Sharfstein also quoted FDA’s oft-repeated statement that the Agency is aware of faulty tests that may have led to “patients being over- or under-treated for heart disease; cancer patients being exposed to inappropriate therapies or not getting effective therapies; incorrect diagnoses of autism; unnecessary antibiotic treatments; and exposure to unnecessary harmful treatments for certain diseases such as Lyme Disease.”

Anti-Regulation Opinion

The counter argument was provided by James Evans and Michael Watson, of UNC Chapel Hill and the American College of Medical Genetics and Genomics respectively. The points made against regulation were consistent with prior arguments that have been made by multiple parties, and but were perhaps even more bold in their statements regarding adverse effects. The authors paint a picture in which large labs might dominate due their sole ability to afford the costs associated with FDA approval.

They support this conjecture with the statement that “In this current debate, small laboratories, academics, and professional organizations are arguing against increased, restrictive regulation, whereas large commercial entities that generally oppose regulation are in favor of the FDA’s action because it is likely to be financially beneficial for them.” I wish that the authors had cited specific examples of large commercial labs expressing support for regulation, as I haven’t been able to find any from either Quest or Labcorp, and neither seem to be on the agenda for the two-day FDA workshop on LDT regulation, to whit…

FDA Workshop

FDA has organized a workshop that runs today and tomorrow, the purpose of which is stated by FDA to be “to obtain feedback from all stakeholders on FDA’s proposal so that it can be refined in the best interest of public health.”

Dozens of stakeholders are slated to present, each with a 4 minute slot, so lots of opinions will be heard. It will be interesting to see if any new points are made, or more importantly, data provided to substantiate previously-made points, as data have been in short supply on both sides of the discussion to-date.